Citations

Abstract Background: Aging, body composition, and sex steroids jointly determine GH production. However, the actions of any given factor are confounded by the effects of the other two. Hypothesis: Age and abdominal visceral fat (AVF) mass govern GH secretion via individually distinctive mechanisms, which can be unmasked by short-term sex steroid deprivation. Design/Subjects: In a university setting, healthy pre- and postmenopausal volunteers underwent GnRH agonist-induced down-regulation for 6 wk to deplete ovarian sex steroids. GH secretion was evaluated by frequent blood sampling, saline vs. dual secretagogue infusions, an irregularity statistic, variable waveform deconvolution analysis, and a simplified feedback model. Computerized tomography was used to estimate AVF mass. Outcomes/Measures: In the sex steroid-deficient milieu, postmenopausal compared with premenopausal women exhibited 1) lower concentrations of IGF-I (P = 0.028) and GH (P < 0.05); 2) reduced pulsatile, but elevated basal, GH secretion (P < 0.05); 3) more irregular GH patterns (P = 0.027); 4) an attenuated GH response to simultaneous GHRH/GH-releasing peptide-2 stimulation (P < 0.01); and 5) more rapid onset of GH release within secretory bursts (P < 0.01). In contrast, AVF negatively forecast GH responses to l-arginine/GH-releasing peptide-2 (r2 = 0.45; P < 0.001) and l-arginine/GHRH (r2 = 0.57; P = 0.007). From these marked contrasts, model-based analyses predicted distinguishable mechanisms by which aging and AVF alter pulsatile GH production. Conclusion: Under limited confounding by sex steroids, age and body composition modulate GH secretion via highly selective peptidyl pathways in healthy women.

Purpose: The purpose of this article is to determine the response rate and toxicity of PCV administered before radiation therapy in patients with newly diagnosed LGO/LGOA and to explore correlations between response with 1p/19q deletions and aberrant p53 expression. Background: Despite prolonged survival of patients with low-grade oligodendroglioma (LGO) and oligoastrocytoma (LGOA), the majority will succumb to progressive disease. Because procarbazine, lomustine (CCNU), and vincristine (PCV) is active in patients with recurrent LGO/LGOA, we hypothesized that it would be beneficial as primary therapy. Methods: Adult patients with residual tumor on magnetic resonance imaging scan following biopsy or subtotal resection of LGO/LGOA received up to six cycles of PCV. Radiation therapy (59.4 or 54.0 Gy) began within 10 weeks of completing chemotherapy or immediately if there was evidence of tumor progression on PCV. Tumor tissue was analyzed by fluorescent in situ hybridization for 1p and 19q deletion and by immunohistochemistry for p53 expression. Results: Eight of 28 (29%) and 13 of 25 (52%) eligible patients demonstrated tumor regression as assessed by the treating physician and a blinded central neuroradiology reviewer, respectively. Myelosuppression was the predominant toxicity. Loss of 1p and 19q were associated with LGO but not LGOA (P = .009), were inversely associated with p53 detection, and were not associated with response to PCV (possibly because of the small sample size). Conclusion: PCV produces tumor regressions in a meaningful proportion of patients with LGO/LGOA. Toxicity, especially myelosuppression, is significant. Loss of 1p and 19q seems limited to patients with pure LGO and is inversely related to p53 alterations.